title: Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells.
abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA1 and LPA3 siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.
authors.affiliation: Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Chu-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Chuan-En
authors.initials: CE
authors.lastname: Lin
authors.forename: Yueh-Chien
authors.initials: YC
authors.lastname: Lin
authors.forename: Tsai-Kai
authors.initials: TK
authors.lastname: Ju
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.forename: Ming-Shyue
authors.initials: MS
authors.lastname: Lee
authors.forename: Jiun-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D010738:Type C Phospholipases / Q000096:biosynthesis
chemical_list: D008246:Lysophospholipids; D017382:Reactive Oxygen Species; D049368:Receptors, Lysophosphatidic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases; C032881:lysophosphatidic acid
keywords: LPA; PKC; Prostate cancer; ROS